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Anti-Phospholipase A2 Receptor Antibody Trajectories for Predicting Prognosis in Patients with Phospholipase A2
Siwen Gong1, Dacheng Chen1, Feng Xu1
1National Clinical Research Center of Kidney Diseases, Jinling Hospital, The First School of Clinical Medicine, Southern Medical University, Nanjing, China.
Introduction:
Phospholipase A2 receptor (PLA2R) is the major autoantigen in membranous nephropathy (MN); however, the trajectories of anti-PLA2R antibodies and their prognostic implications remain unclear.
Methods:
In this retrospective cohort study, we analyzed 1,528 patients with PLA2R-associated MN (2011-2022), each with at least three serial measurements of anti-PLA2R antibody levels. Group-based trajectory modeling was applied to identify distinct longitudinal patterns of antibody change. Associations between antibody trajectories and clinical outcomes were assessed using multivariable Cox proportional hazards and logistic regression models, complemented by Kaplan-Meier analysis.
Results:
Four distinct serum anti-PLA2R antibody trajectories were identified: rising (5.3%), low-stable (74.8%), declining (14.9%), and high-stable (5.0%). The low-stable group had the lowest rates of renal function decline (15.3%), clinical non-remission (18.8%), and relapse (31.6%). Compared to this group, the risks of renal function decline were significantly higher in the rising (adjusted hazard ratio [aHR] = 3.69; 95% confidence interval [CI]: 2.57-5.30), declining (aHR = 1.66; 95% CI: 1.24-2.21), and high-stable (aHR = 4.18; 95% CI: 2.91-6.00) groups. Similarly, the rates of clinical remission were significantly lower (aHR = 0.38 for rising; aHR = 0.61 for declining; aHR = 0.28 for high-stable), while the odds of relapse were higher (adjusted odds ratio 3.13, 2.35, and 3.17, respectively) in these three groups. These associations remained consistent across sex and age subgroups.
Conclusion:
Serum anti-PLA2R antibody trajectories represent a robust prognosis biomarker in MN, useful for risk stratification and clinical decision-making. Patients with high-stable or rising antibody trajectories require heightened clinical attention due to significantly increased risks of renal function decline, clinical non-remission, and relapse.
Insights
Distinct anti-PLA2R antibody trajectories in membranous nephropathy (MN) predict kidney outcomes. Patients with rising or high-stable antibody levels face higher risks of kidney function decline, non-remission, and relapse.
Area of Science:
- Nephrology
- Immunology
- Clinical Biomarkers
Background:
- Phospholipase A2 receptor (PLA2R) is the primary autoantigen in PLA2R-associated membranous nephropathy (MN).
- The longitudinal patterns and prognostic significance of anti-PLA2R antibody levels in MN remain incompletely understood.
Purpose of the Study:
- To identify distinct trajectories of serum anti-PLA2R antibody levels in patients with MN.
- To evaluate the association between these antibody trajectories and clinical outcomes, including renal function decline, remission, and relapse.
Main Methods:
- Retrospective cohort study of 1,528 MN patients with at least three serial anti-PLA2R antibody measurements (2011-2022).
- Group-based trajectory modeling (GBTM) was used to define antibody patterns.
- Multivariable Cox regression and logistic regression models assessed associations with clinical outcomes.
Main Results:
- Four anti-PLA2R antibody trajectories were identified: low-stable (74.8%), declining (14.9%), rising (5.3%), and high-stable (5.0%).
- The low-stable group exhibited the most favorable outcomes (lowest renal decline, non-remission, relapse rates).
- Rising, declining, and high-stable trajectories were significantly associated with increased risk of renal function decline, lower remission rates, and higher relapse rates compared to the low-stable group.
Conclusions:
- Serum anti-PLA2R antibody trajectories serve as a robust prognostic biomarker in MN for risk stratification.
- Patients with high-stable or rising anti-PLA2R antibody levels require close monitoring due to elevated risks of adverse kidney outcomes.
